Phase I/II study of the tumour-targeting human monoclonal antibody-cytokine fusion protein L19-TNF in patients with advanced solid tumours

J Cancer Res Clin Oncol. 2013 Mar;139(3):447-55. doi: 10.1007/s00432-012-1327-7. Epub 2012 Nov 17.


Purpose: L19-TNF is an armed antibody that selectively targets human TNF to extra domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in-man trial with L19-TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity.

Methods: Six cohorts of patients were treated with increasing (1.3-13 μg/kg) doses of intravenous L19-TNF on day 1, 3, and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated at 13 μg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA plasma levels as well as safety and clinical activity were analysed.

Results: Thirty-four patients received at least one L19-TNF dose. The serum half-life of L19-TNF at 13 μg/kg was 33.6 min, and maximum peak serum concentration was 73.14 μg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting toxicity found in one patient. Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients.

Conclusions: Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13 μg/kg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19-TNF possibly in combination with chemotherapy.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / chemistry
  • Cohort Studies
  • Cytokines / administration & dosage
  • Cytokines / chemistry
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Recombinant Fusion Proteins / administration & dosage*


  • Antibodies, Monoclonal
  • Cytokines
  • L19mTNFalpha protein
  • Recombinant Fusion Proteins